Decitabine Followed by a Cancer Antigen Vaccine for Patients With Neuroblastoma and Sarcoma

This study is currently recruiting participants.
Verified December 2013 by University of Louisville
Sponsor:
Collaborator:
Solving Kids’ Cancer
Information provided by (Responsible Party):
Kenneth Lucas, University of Louisville
ClinicalTrials.gov Identifier:
NCT01241162
First received: November 15, 2010
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

This treatment study for relapsed high-risk neuroblastoma, Ewings sarcoma, osteogenic sarcoma, rhabdomyosarcoma or synovial sarcoma involves an autologous cancer testis (CT) antigen specific dendritic cell (DC) vaccine preceded by decitabine as a demethylating chemotherapy.


Condition Intervention Phase
Neuroblastoma
Ewings Sarcoma
Osteogenic Sarcoma
Rhabdomyosarcoma
Synovial Sarcoma
Biological: Autologous dendritic cell vaccine with adjuvant
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial Combining Decitabine and Vaccine Therapy for Patients With Relapsed Neuroblastoma and Sarcoma.

Resource links provided by NLM:


Further study details as provided by University of Louisville:

Primary Outcome Measures:
  • Tolerance of study treatment [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Tolerance to DAC, at at least 50% dosing, and 3 of the 4 planned vaccinations during the first two cycles.


Secondary Outcome Measures:
  • Tumor Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assessment of tumor responses--complete or partial remission, stable disease, and disease progression--by CT/PET/MIBG or MRI after cycles 2 and 4.

  • Immune Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assessment of post-vaccination T cell responses to MAGE-A1, MAGE-A3, and NY-ESO-1 by immunoassays.


Estimated Enrollment: 15
Study Start Date: August 2010
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm study
Biological/Vaccine: Autologous dendritic cell vaccine with adjuvant
Biological: Autologous dendritic cell vaccine with adjuvant

Week 1:

Decitabine (DAC): 10 mg/m2/day IV (Mon-Fri)

Weeks 2 and 3:

Vaccine: 3-5 E6 peptide pulsed DC (Mon)

Imiquimod applied topically to vaccine site before and after vaccination

Other Names:
  • Decitabine (trade name Dacogen or 5-aza-2'-deoxycytidine/DAC
  • Imiquimod (trade name Aladara)

Detailed Description:

For vaccine production, mature DC will be pulsed with overlapping peptides mixes derived from full-length NY-ESO-1, MAGE-A1, and MAGE-A3.

  Eligibility

Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of relapsed high-risk neuroblastoma,Ewings sarcoma, osteogenic sarcoma, rhabdomyosarcoma, synovial sarcoma
  • Patient may have gross tumor that has been treated with multi-agent chemotherapy prior study entry, but does not need to have gross tumor prior to study entry.
  • Patients must have had a diagnosis of neuroblastoma or sarcoma either by histological verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
  • Have received standard chemotherapy and/or SCT, and are at least 6 months post-transplant.
  • Age: Patients must be 1 - < 18 years of age when registered on study.
  • Organ Function Requirements: All patients must have adequate organ function defined as:
  • Hematological Function: ANC ≥ 500; Platelet count ≥ 75.
  • Renal Function: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR A maximum serum creatinine (mg/dL) based on age/gender as follows: 1YO M&F = 0.6, 2-5YO M&F = 0.8, 6-9YO M&F = 1, 10-12YO M&F = 1.2, 13-15YO M = 1.5, 13-15YO F = 1.4, 16+ M = 1.7, 16+ F = 1.4
  • Cardiac Function: Patient must have normal cardiac function documented by Ejection fraction (> 55%) documented by echocardiogram or radionuclide MUGA evaluation OR Fractional shortening (≥ 28%) documented by echocardiogram
  • Liver Function: Total bilirubin ≤ 1.5 x normal for age, AND SGPT (ALT) and SGOT (AST) ≤ 3 x normal for age.
  • Room air pulse oximetry >94%.
  • Male and female sexually active patients of reproductive age who wish to participate must agree to use acceptable contraception.
  • Lansky performance scale > 70, ECOG < 2 (Appendix I).

Exclusion Criteria:

  • Patient is pregnant.
  • Patients with a positive result for any of the following diagnostic tests: Hep B Ag, Hep B Core Ab, Hep C Ab, HIV-1 Ab, HIV-2 Ab, HTLV-1 Ab, HTLV-2 Ab, RPR.
  • Patient has a history of autoimmune disease, specifically inflammatory bowel disease, systemic lupus erythematosis, or rheumatoid arthritis.
  • Patient is receiving concurrent systemic steroid therapy.
  • Patient has a known systemic hypersensitivity to DAC, imiquimod, or any vaccine component.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01241162

Contacts
Contact: Kenneth G Lucas, MD 502-582-0043 k0luca01@louisville.edu
Contact: Deepa Kolaseri, Ph.D 502-582-2447 d.kolaserikrishnadas@louisville.edu

Locations
United States, Kentucky
University of Louisville, Kosair Children's Charities Pediatric Clinical Research Unit Recruiting
Louisville, Kentucky, United States, 40202
Contact: Kenneth G. Lucas, MD    502-852-0043    k0luca01@louisville.edu   
Contact: Janice E Sullivan, MD    502-629-5820    sully@louisville.edu   
Principal Investigator: Kenneth G. Lucas, MD         
Sponsors and Collaborators
University of Louisville
Solving Kids’ Cancer
Investigators
Principal Investigator: Kenneth G Lucas, MD University of Louisville, Kosairs Children Charities Pediatric Clinical Research Unit
  More Information

No publications provided

Responsible Party: Kenneth Lucas, Professor of Pediatrics, University of Louisville
ClinicalTrials.gov Identifier: NCT01241162     History of Changes
Other Study ID Numbers: 34183
Study First Received: November 15, 2010
Last Updated: December 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Louisville:
Neuroblastoma
Ewings sarcoma
osteogenic sarcoma
rhabdomyosarcoma
synovial sarcoma
high-risk
relapsed
children

Additional relevant MeSH terms:
Neuroblastoma
Osteosarcoma
Rhabdomyosarcoma
Sarcoma, Synovial
Sarcoma, Ewing's
Sarcoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Myosarcoma
Neoplasms, Muscle Tissue
Decitabine
Imiquimod
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on April 22, 2014